Since the metabolic activation of anthracycline antibiotics appears to be critical to the action and the toxicity of these agents, we have continued our investigations on the mechanisms of these activations. First, in comparison of structure activity relationships we are examining class I and class II anthracyclines. We find an increased ability of class II anthracyclines (marcellomycin and aclacinomycin) to be metabolized to nonfluorescent metabolites over class I anthracyclines (daunorubicin) by both rat liver cytosol and purified milk xanthine oxidase. We also examined in vivo metabolism of menogarol, a new anthracycline in Phase 1 trials, and found six metabolites. The major metabolite is N-demethylmenogarol. In attempts to develop means to alleviate adriamycin toxicity we are using specific chemical reagents to inactivate these drugs. Peliminary mouse experiments have yielded promising results.